Cancer chemotherapeutics conventionally used include alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, plant-derived agents such as taxol, vincristine and etoposide, as well as metal complexes such as cisplatin. However, none of these substances can be regarded as having a sufficient anti-tumor effect; there has been a strong demand for the development of new anti-tumor agents.
In recent years, sulfonamide-including compounds have been reported as useful anti-tumor agents(1-4). Among them, N-(3-chloro-1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide (hereinafter also referred to as E7070), N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide (hereinafter also referred to as E7820), N-[[(4-chlorophenyl)-amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide (hereinafter also referred to as LY186641), N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide (hereinafter also referred to as LY295501), N-(2,4-dichlorobenzoyl)-4-chlorophenyl-sulfonamide (hereinafter also referred to as LY-ASAP), N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide (hereinafter also referred to as LY573636), 2-sulfanylamido-5-chloroquinoxaline (hereinafter also referred to as CQS) and the like are found to be active against various types of tumors and hence very useful.
Likewise, the anti-VEGF antibody bevacizumab has been reported as an antibody inhibiting angiogenesis(5).
Previous studies have reported that the combined use of a sulfonamide-including compound and an angiogenesis inhibitor produces excellent angiogenesis inhibitory activity and anti-tumor activity(6). However, there has been no report on whether a combination of a sulfonamide-including compound and bevacizumab produces any effect; various documents say nothing about this combination(6).
In recent years, methods have been established for simultaneously detecting the expression levels of many genes using various DNA microarrays, and DNA microarrays are applied to a wide range of purposes(7-8). Likewise, several reports have been made on studies in which DNA microarrays (In part, there is macroarray which uses membrane filters) are used to detect changes in gene expression caused when tumor cells are treated with anti-cancer agents(9-11). These reports indicate that the analysis of gene expression changes is very useful in comprehensively studying, at the molecular level, property comparison of a plurality of cell populations and biological changes in cells caused by treatment with drugs, etc.
In addition, there are other reports in which 60 types of cancer cell line panels from the US National Cancer Institute are reclassified and examined for their properties based on the analysis of their gene expression profiles(12) and in which these 60 types of cancer cell line panels are further studied for the relationship between their gene expression profiles and the susceptibility of each cell line to various anti-cancer agents(13).